CTCs obtained through liquid biopsies show promise as a tool for studying primary and metastatic tumors. CTCs open access to the genetic makeup and protein architecture of the primary and secondary tumors without an invasive biopsy. The identification of CTCs enables physicians to better diagnose specific cancer types or stages as well as tailor treatment protocols specific to a particular patient. These cells are rare in the blood and they range from 1-100 CTCs/ml of whole blood. Challenges in isolating the CTCs involve processing large volumes of blood in a time effective manner and concentrating cells of interest into manageable volumes for analysis. Additionally, in order to perform cost-effective genomic analysis, highly pure samples are needed with low background noise from white blood cells. Immunomagnetic bead-based separation of CTCs generally uses EpCAM antibodies; however this technique misses any CTCs which have undergone Epithelial to Mesenchymal Transition due to EpCAM down regulation. Existing CTC isolation technologies that rely on physical properties of CTCs such as size based filtration, acoustic wave deflection, dielectrophoresis and size based inertial separation are still limited in throughput, pre-processing steps such as RBC-lysis and low sample purity.
More recently, a microfluidic-based device called the Vortex Chip (Vortex Biosciences, Inc., Menlo Park, Calif.) has demonstrated an ability to use high throughput inertial microfluidics and microscale vortices to passively enrich large cells such as CTCs at high purity from large volumes of blood. This same Vortex Chip device is able to capture and enrich beads. The Vortex Chip device captures CTCs (or large particles such as beads) using a series of specially-designed expansion regions that are serially arranged along one or more microfluidic channels. Vortices are generated within the expansion regions and can be used to selectively isolate or trap CTCs or beads from a fluid flow containing the same. For example, U.S. Pat. No. 9,133,499 describes a method and device for isolating cells from a heterogeneous solution using microfluidic trapping vortices. The trapped CTCs and/or beads can be later released from the Vortex Chip for downstream processing or analysis.
Various microfluidic devices for the capture of cells have also been developed. For example, U.S. Patent Application Publication No. 2012-0125842 describes a microfluidic system for the encapsulation of elements including cells that uses two immiscible phases to create capsules or droplets that contain cells. Another example is disclosed in U.S. Pat. No. 8,263,023 which discloses a microfluidic-based system for the sorting and automated encapsulation of cell clusters such as islets of Langerhans. Moreover, while cell encapsulation using emulsions has been performed, this has required the use of a separate immiscible phase co-flow system to create the droplets. This makes the system more complicated and increases the costs for additional pumps, valves, and the like. In addition, other droplet generation devices have used complicated angled structures that are difficult to manufacture in microfluidic devices such as that disclosed in Dangla et al., Droplet microfluidics driven by gradients of confinement, PNAS, vol. 110, no. 3 853-58 (2013).